Disease/Drug of interest: Lujo Virus and Ribavirin
Motivation and Background:
Lujo Virus is a single-stranded virus from the Arenaviridae family. This family of viruses is commonly associated with rodent-transmitted diseases in humans. Lujo Virus can be transmitted through direct contact with an infected rodent, inhalation of infected rodent urine and feces, and/or through contact with a person already infected [1]. This virus was first discovered in September of 2008, after a nosocomial outbreak of five people in Johannesburg, South Africa. The exact event that led to the infection of the first person is unknown. However, once this person was hospitalized, they further infected four health care workers. Lujo Virus leads to Lujo Hemorrhagic Fever (LUHF), whose symptoms include morbilliform rash and swelling of the face and neck, pharyngitis, and diarrhea [1,2]. After an incubation period of one to two weeks, the clinical course is commenced with a nonspecific febrile illness along with headache and muscle pain. The only patient given the drug Ribavirin was also the only person to survive the outbreak. This outbreak bore great resemblance to the 1969 outbreak of Lassa Virus, another virus in the Arenaviridae family that produces similar symptoms and broke out in a nearby region of West Africa. [1,2]. Lassa Virus also leads to a hemorrhagic fever, called Lassa Fever. The Lassa virus however, infects and kills more people annually; estimates show that 100,000 to 300,000 people are infected each year with 5,000 deaths. Those hospitalized with Lassa Fever, like LUHF, are given Ribavirin and, if given soon enough, recover quickly. Lassa Virus is much more common than Lujo Virus. Since the initial outbreak of five people infected with the virus, there has not been any more reports or widespread breakouts of Lujo Virus. LUHF occurs in Southern Africa and those most susceptible to the virus would be field workers because of their heightened exposure to rodents. Due to the relatively resource-poor and politically unstable climate of the regions where Lujo and Lassa Virus were discovered, there has been little opportunity to study the virus in-depth [2,3]. Studying both Lujo and Lassa Virus would allow researchers to understand more the mechanisms of not only the viruses themselves, but their relationship with Ribavirin, the drug used to treat the two infections. Ribavirin’s mechanisms in targeting and treating infections is still a mystery. Furthermore, in case of discoveries of more arenaviruses, understanding the drug’s relationship to this family of viruses would be monumental in preventing and handling widespread breakouts; although Lujo Virus is not common, there are many arenaviruses today, like Lassa Virus, that infect thousands annually. Funding this study also may lead to easier, cheaper, and environmentally-friendly ways to produce the drug, which is used to treat many other viruses outside the arenaviridae family, and allow those in regions vulnerable to viral infections effortless access to treatment and decrease fatality rates.
Arenaviruses are round, oval, or pleomorphic enveloped particles that contain two RNA segments of virus origin and ribosome-like components with a mean diameter of 110 to 130 nm. Figure 1 shows the typical structure of an arenavirus. The genome of an arenavirus is completely made out of RNA. It’s replication mechanism is not quite understood but it is known that new viral particles, called virions, are produced through budding of the surface of their hosts' cells. Lujo virus is categorized as an Old World Arenavirus, meaning it first infects rodents in the Eastern hemisphere.
Size: molecular weight of the protein
Location:
Function in a normal cell: The virus affects the vascular system and can give multisystemic illnesses in patients.
Figure 1. Close up of an arenavirus. Arenaviruses can be round, oval, or pleomorphic in its shape.
Drug Information:
Schematic figure of drug:
figure
Figure 2. Structure of ribavirin and two similar molecules
Figure 3. Ball-and-stick model of Ribavirin molecule
Formula: C8H12N4O5
Molecular weight: 244.206 g/mol
CAS Number: 36791-04-5
Delivery method: Ribavirin can be administered orally, intravenously or through inhalation, depending on the viral pathogen.
Side effects: The list of side effects for Ribavirin is extensive and broad; the most common side effects found were fatigue, hemolytic anemia, decreased hemoglobin, insomnia, dyspnea, lack of concentration, emotional lability, and irritability. Ribavirin cannot be taken while someone is pregnant or plans to within six months, with the same going for fathers.
Other names: Ribavirin is also sold under different names including Rebetol, Copegus, Ribasphere and Virazole.
Maker or company: Ribavirin is manufactured through multiple companies in the United States, such as Genentech and Kadmon Pharmaceuticals.
Is it patented? The patent for Ribavirin in the U.S. expired in September of 2001, thus opening the door for generic Ribavirin.
Clinical Trials Info: There are a total of 1046 clinical trials with Ribavirin that are either ongoing, completed, or have been terminated.
Origin: Ribavirin was first discovered and developed in 1970 by researchers from Valeant Pharmaceuticals. Ribavirin can be produced through different ways including synthetic, enzymatic, and fermentation; the most common method is chemical synthesis.
Alternatives to this drug: A side effect of Ribavirin is anaemia. Erythropoietin or Taribavirin may be used instead to avoid anaemia. Other uses: can this drug be used to treat other diseases/conditions?
Ribavirin has been shown to be effective for other arenaviruses and viral hemorrhagic fevers and shows promises for hepatitis C therapy.
Disease/Drug of interest: Lujo Virus and Ribavirin
Motivation and Background:
Lujo Virus is a single-stranded virus from the Arenaviridae family. This family of viruses is commonly associated with rodent-transmitted diseases in humans. Lujo Virus can be transmitted through direct contact with an infected rodent, inhalation of infected rodent urine and feces, and/or through contact with a person already infected [1]. This virus was first discovered in September of 2008, after a nosocomial outbreak of five people in Johannesburg, South Africa. The exact event that led to the infection of the first person is unknown. However, once this person was hospitalized, they further infected four health care workers. Lujo Virus leads to Lujo Hemorrhagic Fever (LUHF), whose symptoms include morbilliform rash and swelling of the face and neck, pharyngitis, and diarrhea [1,2]. After an incubation period of one to two weeks, the clinical course is commenced with a nonspecific febrile illness along with headache and muscle pain. The only patient given the drug Ribavirin was also the only person to survive the outbreak.This outbreak bore great resemblance to the 1969 outbreak of Lassa Virus, another virus in the Arenaviridae family that produces similar symptoms and broke out in a nearby region of West Africa. [1,2]. Lassa Virus also leads to a hemorrhagic fever, called Lassa Fever. The Lassa virus however, infects and kills more people annually; estimates show that 100,000 to 300,000 people are infected each year with 5,000 deaths. Those hospitalized with Lassa Fever, like LUHF, are given Ribavirin and, if given soon enough, recover quickly. Lassa Virus is much more common than Lujo Virus. Since the initial outbreak of five people infected with the virus, there has not been any more reports or widespread breakouts of Lujo Virus. LUHF occurs in Southern Africa and those most susceptible to the virus would be field workers because of their heightened exposure to rodents. Due to the relatively resource-poor and politically unstable climate of the regions where Lujo and Lassa Virus were discovered, there has been little opportunity to study the virus in-depth [2,3].
Studying both Lujo and Lassa Virus would allow researchers to understand more the mechanisms of not only the viruses themselves, but their relationship with Ribavirin, the drug used to treat the two infections. Ribavirin’s mechanisms in targeting and treating infections is still a mystery. Furthermore, in case of discoveries of more arenaviruses, understanding the drug’s relationship to this family of viruses would be monumental in preventing and handling widespread breakouts; although Lujo Virus is not common, there are many arenaviruses today, like Lassa Virus, that infect thousands annually. Funding this study also may lead to easier, cheaper, and environmentally-friendly ways to produce the drug, which is used to treat many other viruses outside the arenaviridae family, and allow those in regions vulnerable to viral infections effortless access to treatment and decrease fatality rates.
References:
[1] Arenaviridae https://www.cdc.gov/vhf/virus-families/arenaviridae.html (accessed Feb 4, 2017).
[2] Lujo hemorrhagic fever (LUHF) https://www.cdc.gov/vhf/lujo/index.html (accessed Feb 4, 2017).
[3] Lassa Fever https://www.cdc.gov/vhf/lassa/index.html (accessed Feb 4, 2017)
External links:
Target Information:
Arenaviruses are round, oval, or pleomorphic enveloped particles that contain two RNA segments of virus origin and ribosome-like components with a mean diameter of 110 to 130 nm. Figure 1 shows the typical structure of an arenavirus. The genome of an arenavirus is completely made out of RNA. It’s replication mechanism is not quite understood but it is known that new viral particles, called virions, are produced through budding of the surface of their hosts' cells. Lujo virus is categorized as an Old World Arenavirus, meaning it first infects rodents in the Eastern hemisphere.Size: molecular weight of the protein
Location:
Function in a normal cell: The virus affects the vascular system and can give multisystemic illnesses in patients.Figure 1. Close up of an arenavirus. Arenaviruses can be round, oval, or pleomorphic in its shape.
Drug Information:
Schematic figure of drug:
Figure 2. Structure of ribavirin and two similar molecules
Figure 3. Ball-and-stick model of Ribavirin molecule
Formula: C8H12N4O5
Molecular weight: 244.206 g/mol
CAS Number: 36791-04-5
Delivery method: Ribavirin can be administered orally, intravenously or through inhalation, depending on the viral pathogen.
Side effects: The list of side effects for Ribavirin is extensive and broad; the most common side effects found were fatigue, hemolytic anemia, decreased hemoglobin, insomnia, dyspnea, lack of concentration, emotional lability, and irritability. Ribavirin cannot be taken while someone is pregnant or plans to within six months, with the same going for fathers.
Other names: Ribavirin is also sold under different names including Rebetol, Copegus, Ribasphere and Virazole.
Maker or company: Ribavirin is manufactured through multiple companies in the United States, such as Genentech and Kadmon Pharmaceuticals.
Is it patented? The patent for Ribavirin in the U.S. expired in September of 2001, thus opening the door for generic Ribavirin.
Clinical Trials Info: There are a total of 1046 clinical trials with Ribavirin that are either ongoing, completed, or have been terminated.
Origin:
Ribavirin was first discovered and developed in 1970 by researchers from Valeant Pharmaceuticals. Ribavirin can be produced through different ways including synthetic, enzymatic, and fermentation; the most common method is chemical synthesis.
Alternatives to this drug: A side effect of Ribavirin is anaemia. Erythropoietin or Taribavirin may be used instead to avoid anaemia.
Other uses: can this drug be used to treat other diseases/conditions?
Ribavirin has been shown to be effective for other arenaviruses and viral hemorrhagic fevers and shows promises for hepatitis C therapy.